Magnetovaccination as a Novel Method to Assess and Quantify Dendritic Cell Tumor Antigen Capture and Delivery to Lymph Nodes
A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use...
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| Published in | Cancer research (Chicago, Ill.) Vol. 69; no. 7; pp. 3180 - 3187 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Philadelphia, PA
American Association for Cancer Research
01.04.2009
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0008-5472 1538-7445 1538-7445 |
| DOI | 10.1158/0008-5472.CAN-08-3691 |
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| Abstract | A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of superparamagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ, to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell–based vaccine that was irradiated and labeled with SPIO. APCs that had captured SPIO were imaged over time as they accumulated in LNs. We show here that MRI is capable of monitoring, in vivo, the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo. Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers. [Cancer Res 2009;69(7):3180–7] |
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| AbstractList | A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of superparamagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ, to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell-based vaccine that was irradiated and labeled with SPIO. APCs that had captured SPIO were imaged over time as they accumulated in LNs. We show here that MRI is capable of monitoring, in vivo, the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo. Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers.A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of superparamagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ, to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell-based vaccine that was irradiated and labeled with SPIO. APCs that had captured SPIO were imaged over time as they accumulated in LNs. We show here that MRI is capable of monitoring, in vivo, the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo. Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers. A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of superparamagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ, to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell-based vaccine that was irradiated and labeled with SPIO. APCs that had captured SPIO were imaged over time as they accumulated in LNs. We show here that MRI is capable of monitoring, in vivo, the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo. Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers. A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of superparamagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ, to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell–based vaccine that was irradiated and labeled with SPIO. APCs that had captured SPIO were imaged over time as they accumulated in LNs. We show here that MRI is capable of monitoring, in vivo, the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo. Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers. [Cancer Res 2009;69(7):3180–7] A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of super-paramagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ , to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell–based vaccine that was irradiated and labeled with SPIO. APCs that had captured SPIO were imaged over time as they accumulated in LNs. We show here that MRI is capable of monitoring, in vivo , the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo . Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers. |
| Author | Long, Christopher M. Levitsky, Hyam I. van Laarhoven, Hanneke W.M. Bulte, Jeff W.M. |
| AuthorAffiliation | 4 Department of Chemical and Biomolecular Engineering, Johns Hopkins University School of Medicine Baltimore, Maryland 1 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 6 Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands 3 Russel H. Morgan Department of Radiology, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 5 Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine Baltimore, Maryland 2 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland |
| AuthorAffiliation_xml | – name: 4 Department of Chemical and Biomolecular Engineering, Johns Hopkins University School of Medicine Baltimore, Maryland – name: 3 Russel H. Morgan Department of Radiology, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, Maryland – name: 1 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland – name: 2 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland – name: 5 Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine Baltimore, Maryland – name: 6 Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands |
| Author_xml | – sequence: 1 givenname: Christopher M. surname: Long fullname: Long, Christopher M. – sequence: 2 givenname: Hanneke W.M. surname: van Laarhoven fullname: van Laarhoven, Hanneke W.M. – sequence: 3 givenname: Jeff W.M. surname: Bulte fullname: Bulte, Jeff W.M. – sequence: 4 givenname: Hyam I. surname: Levitsky fullname: Levitsky, Hyam I. |
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| Keywords | Performance evaluation Dendritic cell Tumor associated antigen Lymph node Rodentia Method Route of administration Nuclear magnetic resonance imaging Capture In vivo Vertebrata Mammalia Mouse Antigen presenting cell Animal Application method Technique Tumor cell |
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| SubjectTerms | Adjuvants, Immunologic - pharmacology Aminoquinolines - pharmacology Animals Antigen Presentation Antineoplastic agents Biological and medical sciences Cancer Vaccines - immunology Cancer Vaccines - pharmacology Dendritic Cells - immunology Female Ferric Compounds - administration & dosage Ferric Compounds - analysis Granulocyte-Macrophage Colony-Stimulating Factor - immunology Image Processing, Computer-Assisted Imiquimod Lymph Nodes - immunology Magnetic Resonance Imaging - methods Magnetics - methods Medical sciences Melanoma, Experimental - immunology Melanoma, Experimental - metabolism Melanoma, Experimental - therapy Mice Mice, Inbred C57BL Pharmacology. Drug treatments Tumors |
| Title | Magnetovaccination as a Novel Method to Assess and Quantify Dendritic Cell Tumor Antigen Capture and Delivery to Lymph Nodes |
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